High glucose enhances microRNA-26a to activate mTORC1 for mesangial cell hypertrophy and matrix protein expression

Cellular Signalling
Nirmalya DeyG G Choudhury

Abstract

High glucose milieu inhibits PTEN expression to activate Akt kinase and induces glomerular mesangial cell hypertrophy and matrix protein expression in diabetic nephropathy. Specific mechanism by which high glucose inhibits PTEN expression is not clear. We found that high glucose increased the expression of the microRNA-26a (miR-26a) in mesangial cells. Using a sensor plasmid with 3'UTR-driven luciferase, we showed PTEN as a target of miR-26a in response to high glucose. Overexpression of miR-26a reduced the PTEN protein levels resulting in increased Akt kinase activity similar to high glucose treatment. In contrast, anti-miR-26a reversed high glucose-induced suppression of PTEN with concomitant inhibition of Akt kinase activity. Akt-mediated phosphorylation of tuberin and PRAS40 regulates mTORC1, which is necessary for mesangial cell hypertrophy and matrix protein expression. Inhibition of high glucose-induced miR-26a blocked phosphorylation of tuberin and PRAS40, which lead to suppression of phosphorylation of S6 kinase and 4EBP-1, two substrates of mTORC1. Furthermore, we show that expression of miR-26a induced mesangial cell hypertrophy and increased fibronectin and collagen I (α2) expression similar to that observed with th...Continue Reading

References

Oct 28, 2008·Breast Cancer Research and Treatment·Triparna Ghosh-ChoudhuryNandini Ghosh-Choudhury
Jan 12, 2010·Cellular Signalling·Nayana Ghosh-ChoudhuryGoutam Ghosh Choudhury
May 4, 2010·Biogerontology·Johannes GrillariRegina Grillari-Voglauer
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini

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Citations

Nov 15, 2015·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Li XuLining Wang
Apr 14, 2016·International Journal of Molecular Sciences·Maskomani SilambarasanKandiah Jeyaseelan
Jun 5, 2015·Frontiers in Cellular Neuroscience·Juhyun Song, Jong Eun Lee
Jul 8, 2017·Artificial Cells, Nanomedicine, and Biotechnology·Wei-Hong WangSheng-Guang He
Apr 21, 2017·American Journal of Physiology. Renal Physiology·Falguni DasGoutam Ghosh Choudhury
Apr 21, 2020·Critical Reviews in Clinical Laboratory Sciences·Manoj KhokharPraveen Sharma
Oct 6, 2017·Oncotarget·Dan LvLin Huang
Sep 27, 2018·Kidney Research and Clinical Practice·Mitsuo Kato
Nov 6, 2015·American Journal of Physiology. Renal Physiology·Kirti BhattRama Natarajan
Dec 28, 2016·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Jing-Jing YangJun Li
Mar 8, 2017·Oxidative Medicine and Cellular Longevity·Cheng LiJian Sun
Oct 3, 2020·Animal Nutrition·Md Mahmodul Hasan Sohel
Jun 5, 2019·Kidney & Blood Pressure Research·Xiaoyan LiWeiqiang Lin

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